MTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β₁-induced collagen biosynthesis.

ABSTRACT: The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue repair is complete, lead to pathological fibrosis and are also features of the stromal response in cancer. Myofibroblast differentiation is accompanied by changes in cellular metabolism, including increased glycolysis, to meet the biosynthetic demands of enhanced ECM production. Here, we showed that transforming growth factor-β₁ (TGF-β₁), the key pro-fibrotic cytokine implicated in multiple fibrotic conditions, increased the production of activating transc

SUBMITTER: Selvarajah B 

PROVIDER: S-EPMC6584619 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature